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Initiative seeks to develop therapies to combat Ebola

Sep. 18, 2014, 9:15 AM

James Crowe Jr., M.D., right, looks on as graduate student Andrew Flyak adjusts equipment in the Vanderbilt Vaccine Center used in the production of anti-Ebola antibodies. (photo by Anne Rayner)

Vanderbilt University researchers have partnered with Mapp Biopharmaceutical Inc. to develop new human antibody therapies for people exposed to the deadly Ebola and Marburg viruses.

The San Diego-based company has developed an experimental treatment, called ZMapp, which contains antibodies manufactured in plants.  ZMapp has prevented lethal disease in rhesus monkeys but has not yet been tested for safety and efficacy in humans.

At Vanderbilt, researchers are using a high-efficiency method to isolate and generate large quantities of human antibodies from the blood of people who have survived Ebola and Marburg infections and who are now healthy. No live virus is used in the research here.

The goal of the collaboration is to develop safe and effective antibody therapies that can provide short-term protection to health care workers and others at risk of exposure to the two hemorrhagic filoviruses, which kill in part by causing massive bleeding.

“Our laboratory has been isolating antibodies to major human pathogens such as Ebola in order to understand the basic science of immunity in humans,” said lead Vanderbilt researcher James Crowe Jr., M.D., Ann Scott Carrell Professor and director of the Vanderbilt Vaccine Center.

“However, with the current urgent medical need for treatments for Ebola infection, we are thrilled to be working with Mapp Biopharmaceutical to produce the antibodies we have discovered as antiviral drugs that may benefit patients and health care workers facing this terrible epidemic,” Crowe said.

The current Ebola outbreak, which began in West Africa last December, has killed more than 2,500 people, making it the deadliest outbreak since the virus was discovered in 1976. Health officials say the true death toll may be three or four times greater.

“Dr. James Crowe’s success at isolating potent and effective human monoclonal antibodies against a wide range of infectious diseases is well recognized,” said company president Larry Zeitlin, Ph.D. “Mapp Biopharmaceutical is delighted to collaborate with him to develop human therapeutics against a range of public health threats.”

Monoclonal antibodies are made from a single clone of B cells, a type of white blood cell, that have been fused to myeloma (cancer) cells to form fast-growing “hybridomas.” This allows researchers to quickly generate large quantities of antibodies against specific viral targets.

“We’re the only lab in the world that has a high-efficiency human hybridoma technique for isolating human monoclonal antibodies,” Crowe said.

The method, developed over the last 15 years, was instrumental in isolating antibodies from the blood of people who survived the worldwide 1918 influenza pandemic as well as antibodies to avian influenza, dengue and other current viral threats.

Crowe said his 12-person team is currently studying antibody responses to about 30 different viruses. “We’re also working with Vanderbilt collaborators on bacteria — Staph and Clostridium difficile (“C. diff”) infection, a leading cause of hospital-associated diarrhea,” he said.

Vanderbilt’s research on Ebola and Marburg is being conducted in conjunction with the University of Texas Medical Branch in Galveston with support from the U.S. Department of Defense and the National Institutes of Health.

 

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